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Protein

Probable leucine--tRNA ligase, mitochondrial

Gene

LARS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

ATP + L-leucine + tRNA(Leu) = AMP + diphosphate + L-leucyl-tRNA(Leu).

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei642 – 6421ATPBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Aminoacyl-tRNA synthetase, Ligase

Keywords - Biological processi

Protein biosynthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi6.1.1.4. 2681.
ReactomeiREACT_15302. Mitochondrial tRNA aminoacylation.
SABIO-RKQ15031.

Names & Taxonomyi

Protein namesi
Recommended name:
Probable leucine--tRNA ligase, mitochondrial (EC:6.1.1.4)
Alternative name(s):
Leucyl-tRNA synthetase
Short name:
LeuRS
Gene namesi
Name:LARS2
Synonyms:KIAA0028
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:17095. LARS2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Perrault syndrome 4 (PRLTS4)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile.

See also OMIM:615300
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti522 – 5221T → N in PRLTS4; reduced activity. 1 Publication
VAR_070094
Natural varianti629 – 6291T → M in PRLTS4; found in a compound heterozygote also carrying a null mutation; the mutant is functional in a yeast complementaion assay but might be insufficient as a heterozygote with a fully non-functional allele. 1 Publication
VAR_070095

Keywords - Diseasei

Deafness, Disease mutation

Organism-specific databases

MIMi615300. phenotype.
Orphaneti2855. Perrault syndrome.
PharmGKBiPA134982982.

Chemistry

DrugBankiDB00149. L-Leucine.

Polymorphism and mutation databases

BioMutaiLARS2.
DMDMi2501029.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 903Probable leucine--tRNA ligase, mitochondrialPRO_0000035806
Transit peptidei1 – ?MitochondrionSequence Analysis

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei68 – 681N6-acetyllysineBy similarity
Modified residuei236 – 2361N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ15031.
PaxDbiQ15031.
PeptideAtlasiQ15031.
PRIDEiQ15031.

PTM databases

PhosphoSiteiQ15031.

Expressioni

Tissue specificityi

Ubiquitously expressed, but highest expression in tissues with high metabolic rates, such as skeletal muscle, heart, and kidney.1 Publication

Gene expression databases

BgeeiQ15031.
CleanExiHS_LARS2.
ExpressionAtlasiQ15031. baseline and differential.
GenevestigatoriQ15031.

Organism-specific databases

HPAiHPA035951.
HPA045450.

Interactioni

Protein-protein interaction databases

BioGridi116968. 12 interactions.
STRINGi9606.ENSP00000265537.

Structurei

3D structure databases

ProteinModelPortaliQ15031.
SMRiQ15031. Positions 53-901.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi92 – 10211"HIGH" regionAdd
BLAST
Motifi639 – 6435"KMSKS" region

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0495.
GeneTreeiENSGT00390000015114.
HOGENOMiHOG000200747.
HOVERGENiHBG017877.
InParanoidiQ15031.
KOiK01869.
OMAiQSSWYFL.
OrthoDBiEOG754HNN.
PhylomeDBiQ15031.
TreeFamiTF105662.

Family and domain databases

Gene3Di1.10.730.10. 1 hit.
3.40.50.620. 3 hits.
3.90.740.10. 1 hit.
InterProiIPR001412. aa-tRNA-synth_I_CS.
IPR002300. aa-tRNA-synth_Ia.
IPR002302. Leu-tRNA-ligase.
IPR013155. M/V/L/I-tRNA-synth_anticd-bd.
IPR014729. Rossmann-like_a/b/a_fold.
IPR009080. tRNAsynth_1a_anticodon-bd.
IPR009008. Val/Leu/Ile-tRNA-synth_edit.
[Graphical view]
PANTHERiPTHR11946:SF7. PTHR11946:SF7. 1 hit.
PfamiPF08264. Anticodon_1. 1 hit.
PF00133. tRNA-synt_1. 3 hits.
[Graphical view]
PRINTSiPR00985. TRNASYNTHLEU.
SUPFAMiSSF47323. SSF47323. 1 hit.
SSF50677. SSF50677. 1 hit.
TIGRFAMsiTIGR00396. leuS_bact. 1 hit.
PROSITEiPS00178. AA_TRNA_LIGASE_I. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15031-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASVWQRLGF YASLLKRQLN GGPDVIKWER RVIPGCTRSI YSATGKWTKE
60 70 80 90 100
YTLQTRKDVE KWWHQRIKEQ ASKISEADKS KPKFYVLSMF PYPSGKLHMG
110 120 130 140 150
HVRVYTISDT IARFQKMRGM QVINPMGWDA FGLPAENAAV ERNLHPQSWT
160 170 180 190 200
QSNIKHMRKQ LDRLGLCFSW DREITTCLPD YYKWTQYLFI KLYEAGLAYQ
210 220 230 240 250
KEALVNWDPV DQTVLANEQV DEHGCSWRSG AKVEQKYLRQ WFIKTTAYAK
260 270 280 290 300
AMQDALADLP EWYGIKGMQA HWIGDCVGCH LDFTLKVHGQ ATGEKLTAYT
310 320 330 340 350
ATPEAIYGTS HVAISPSHRL LHGHSSLKEA LRMALVPGKD CLTPVMAVNM
360 370 380 390 400
LTQQEVPVVI LAKADLEGSL DSKIGIPSTS SEDTILAQTL GLAYSEVIET
410 420 430 440 450
LPDGTERLSS SAEFTGMTRQ DAFLALTQKA RGKRVGGDVT SDKLKDWLIS
460 470 480 490 500
RQRYWGTPIP IVHCPVCGPT PVPLEDLPVT LPNIASFTGK GGPPLAMASE
510 520 530 540 550
WVNCSCPRCK GAAKRETDTM DTFVDSAWYY FRYTDPHNPH SPFNTAVADY
560 570 580 590 600
WMPVDLYIGG KEHAVMHLFY ARFFSHFCHD QKMVKHREPF HKLLAQGLIK
610 620 630 640 650
GQTFRLPSGQ YLQREEVDLT GSVPVHAKTK EKLEVTWEKM SKSKHNGVDP
660 670 680 690 700
EEVVEQYGID TIRLYILFAA PPEKDILWDV KTDALPGVLR WQQRLWTLTT
710 720 730 740 750
RFIEARASGK SPQPQLLSNK EKAEARKLWE YKNSVISQVT THFTEDFSLN
760 770 780 790 800
SAISQLMGLS NALSQASQSV ILHSPEFEDA LCALMVMAAP LAPHVTSEIW
810 820 830 840 850
AGLALVPRKL CAHYTWDASV LLQAWPAVDP EFLQQPEVVQ MAVLINNKAC
860 870 880 890 900
GKIPVPQQVA RDQDKVHEFV LQSELGVRLL QGRSIKKSFL SPRTALINFL

VQD
Length:903
Mass (Da):101,976
Last modified:November 1, 1997 - v2
Checksum:iD9AC143125124F58
GO

Sequence cautioni

The sequence BAA04877.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti522 – 5221T → N in PRLTS4; reduced activity. 1 Publication
VAR_070094
Natural varianti629 – 6291T → M in PRLTS4; found in a compound heterozygote also carrying a null mutation; the mutant is functional in a yeast complementaion assay but might be insufficient as a heterozygote with a fully non-functional allele. 1 Publication
VAR_070095
Natural varianti727 – 7271K → N.
Corresponds to variant rs36054230 [ dbSNP | Ensembl ].
VAR_052638
Natural varianti831 – 8311E → D.
Corresponds to variant rs9827689 [ dbSNP | Ensembl ].
VAR_052639

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D21851 mRNA. Translation: BAA04877.2. Different initiation.
BC025989 mRNA. Translation: AAH25989.1.
CCDSiCCDS2728.1.
RefSeqiNP_056155.1. NM_015340.3.
XP_005265063.1. XM_005265006.1.
UniGeneiHs.526975.

Genome annotation databases

EnsembliENST00000265537; ENSP00000265537; ENSG00000011376.
ENST00000415258; ENSP00000408576; ENSG00000011376.
GeneIDi23395.
KEGGihsa:23395.
UCSCiuc003cop.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D21851 mRNA. Translation: BAA04877.2. Different initiation.
BC025989 mRNA. Translation: AAH25989.1.
CCDSiCCDS2728.1.
RefSeqiNP_056155.1. NM_015340.3.
XP_005265063.1. XM_005265006.1.
UniGeneiHs.526975.

3D structure databases

ProteinModelPortaliQ15031.
SMRiQ15031. Positions 53-901.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116968. 12 interactions.
STRINGi9606.ENSP00000265537.

Chemistry

DrugBankiDB00149. L-Leucine.

PTM databases

PhosphoSiteiQ15031.

Polymorphism and mutation databases

BioMutaiLARS2.
DMDMi2501029.

Proteomic databases

MaxQBiQ15031.
PaxDbiQ15031.
PeptideAtlasiQ15031.
PRIDEiQ15031.

Protocols and materials databases

DNASUi23395.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265537; ENSP00000265537; ENSG00000011376.
ENST00000415258; ENSP00000408576; ENSG00000011376.
GeneIDi23395.
KEGGihsa:23395.
UCSCiuc003cop.1. human.

Organism-specific databases

CTDi23395.
GeneCardsiGC03P045405.
HGNCiHGNC:17095. LARS2.
HPAiHPA035951.
HPA045450.
MIMi604544. gene.
615300. phenotype.
neXtProtiNX_Q15031.
Orphaneti2855. Perrault syndrome.
PharmGKBiPA134982982.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0495.
GeneTreeiENSGT00390000015114.
HOGENOMiHOG000200747.
HOVERGENiHBG017877.
InParanoidiQ15031.
KOiK01869.
OMAiQSSWYFL.
OrthoDBiEOG754HNN.
PhylomeDBiQ15031.
TreeFamiTF105662.

Enzyme and pathway databases

BRENDAi6.1.1.4. 2681.
ReactomeiREACT_15302. Mitochondrial tRNA aminoacylation.
SABIO-RKQ15031.

Miscellaneous databases

ChiTaRSiLARS2. human.
GeneWikiiLARS2.
GenomeRNAii23395.
NextBioi45533.
PROiQ15031.
SOURCEiSearch...

Gene expression databases

BgeeiQ15031.
CleanExiHS_LARS2.
ExpressionAtlasiQ15031. baseline and differential.
GenevestigatoriQ15031.

Family and domain databases

Gene3Di1.10.730.10. 1 hit.
3.40.50.620. 3 hits.
3.90.740.10. 1 hit.
InterProiIPR001412. aa-tRNA-synth_I_CS.
IPR002300. aa-tRNA-synth_Ia.
IPR002302. Leu-tRNA-ligase.
IPR013155. M/V/L/I-tRNA-synth_anticd-bd.
IPR014729. Rossmann-like_a/b/a_fold.
IPR009080. tRNAsynth_1a_anticodon-bd.
IPR009008. Val/Leu/Ile-tRNA-synth_edit.
[Graphical view]
PANTHERiPTHR11946:SF7. PTHR11946:SF7. 1 hit.
PfamiPF08264. Anticodon_1. 1 hit.
PF00133. tRNA-synt_1. 3 hits.
[Graphical view]
PRINTSiPR00985. TRNASYNTHLEU.
SUPFAMiSSF47323. SSF47323. 1 hit.
SSF50677. SSF50677. 1 hit.
TIGRFAMsiTIGR00396. leuS_bact. 1 hit.
PROSITEiPS00178. AA_TRNA_LIGASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1."
    Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.
    DNA Res. 1:27-35(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Bone marrow.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  3. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-236, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  4. "Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes."
    Li R., Guan M.X.
    Mol. Cell. Biol. 30:2147-2154(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. "Mutations in LARS2, encoding mitochondrial leucyl-tRNA synthetase, lead to premature ovarian failure and hearing loss in Perrault syndrome."
    Pierce S.B., Gersak K., Michaelson-Cohen R., Walsh T., Lee M.K., Malach D., Klevit R.E., King M.C., Levy-Lahad E.
    Am. J. Hum. Genet. 92:614-620(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PRLTS4 ASN-522 AND MET-629, CHARACTERIZATION OF VARIANTS PRLTS4 ASN-522 AND MET-629.

Entry informationi

Entry nameiSYLM_HUMAN
AccessioniPrimary (citable) accession number: Q15031
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 29, 2015
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.